Medicine | The viruses leading to cervical cancer have gone underdiagnosed for too long; now, with a new vaccine, women-and girls-face ethical challenges over making use of it

"Stalking a silent killer" Continued...

Eva Perón never knew what killed her. In the early 1950s, before patients' bills of rights and managed care, doctors and families commonly kept cancer diagnoses a secret from those afflicted. But Argentinian president Juan Perón went to great lengths to hide his wife's diagnosis of cervical cancer from her. He never told his wife before her death in 1952 that an American specialist performed her hysterectomy in place of her local doctor. Historians have speculated that the deception was part political maneuvering and part denial; President Perón did not want the country to learn of his misfortune in an election year, and his wife did not want to know.

But there was something neither Perón nor the public knew about Evita, even after a Broadway musical memorialized the story of her populism and humanitarianism. Her cancer was caused by a sexually transmitted virus that she most likely caught from her husband, whose first wife also died of cervical cancer.

The CDC estimates that 80 percent of women under 50 have had human papillomavirus (HPV), the virus that causes cervical cancer. Doctors have known about the disease for at least 20 years, but until recently it remained as much a mystery to the public as it did to Juan and Eva Perón.

The release of an HPV vaccine in June finally gave women a reason to talk to their doctors and each other about the disease. The facts of HPV challenge what they thought they knew about sex and sexually transmitted diseases (STDs).

HPV can occur in monogamous relationships if one of the people in the relationship has had previous genital contact with someone else. As with all STDs, abstinence until marriage will prevent HPV, but it has to be abstinence from all genital contact, and on the part of both spouses. HPV is similar to HIV, the virus that causes AIDS, only in that both can be transmitted sexually. But statistically speaking, the population that exposes itself to HPV is much larger than the one that exposes itself to HIV. About 40,000 new U.S. cases of HIV occur every year, while there are over 6.2 million new cases of HPV.

There are more than 100 kinds of Human papillomaviruses, all of which cause changes to skin cells. The majority of types cause the common skin wart; about 40 kinds of HPV are transmitted through genital contact. Most HPV infections clear up on their own with no symptoms. Some types of HPV cause genital warts in men and women, while a handful of strains change the cells of the cervix into pre-cancerous cells. The cells will develop into cancer if not detected and removed. Men can carry the kinds of HPV that cause cervical cancer, but they rarely experience any symptoms from it. Doctors now believe HPV is the sole cause of all cervical cancer.

With 6.2 million new cases of HPV every year-more than gonorrhea, chlamydia, and syphilis combined-the Centers for Disease Control predict that if every American ages 14 to 49 took an HPV test on the same day, 15 percent-20 million people-would be infected. More than half of sexually active men and women get HPV at some point in their lives; and, the CDC says, by age 50, 80 percent of women have had HPV. A recent study showed people who use condoms were 70 percent less likely to get HPV than those who do not, but condoms are not 100 percent effective at preventing the virus.

Gynecologists now use HPV testing as a follow-up to an abnormal Pap test, which analyzes cervical cells for early signs of cancer. But HPV has a long, unpredictable latency, so a woman can contract the virus early in her adult life and have it for years before it affects the cells in her cervix. A man can also carry the virus for a long time and never experience symptoms. Without abstinence, both may give the disease to others in the meantime.

Connie Mao, a gynecologist at the Harborview Women's Clinic in Seattle, said most of her patients with HPV had never heard of the virus before she diagnosed them with it. "They want to treat it, they want to know it's gone, and they want to know who gave it to them," said Mao, who is also on the faculty at the University of Washington, the country's leading HPV research center. "All of those questions with HPV are very hard. You could have had it for 10 years, and I can't treat it."

Emily Wyse, a cervical cancer survivor, is still searching for answers since undergoing chemotherapy, radiation, and a hysterectomy a year ago. Before her diagnosis in 2005, Wyse had annual gynecological exams and Pap tests, all of which showed normal cervical cells. When she found out she had cancer, Wyse, 31, had been married for eight years and had two children. Her youngest child was 1 year old.

Wyse had never heard of HPV before her cancer diagnosis, but she soon had read everything she could find about it. She had never been tested for HPV, but she assumed she had it.

"We do not routinely test the cancers for HPV because it does not affect treatment and they are all positive," said Liz Swisher, a gynecological oncologist at the University of Washington, where Wyse was treated. After treatment, Wyse tested negative for HPV.

"There is a possibility that maybe I had the virus, but I was never tested for the virus, and now it's gone," she said.

With her cancer treatment a year behind her, Wyse considers herself an advocate for cervical cancer screening. She took a job as a program assistant at the Seattle Cancer Care Alliance, where she has chances to support other women who are going through cancer treatment. She still wants to reconcile her own story with the facts about cervical cancer and its links to HPV.

Wyse plans to have specimens from some of her old Pap tests checked for HPV. She believes what Swisher and other doctors say about the cause of cervical cancer, but she also wants to understand exactly what happened to her body.

"I'm kind of in limbo at this point. I want to know for sure," Wyse said. She also wants other women to know for sure, which is why she thinks the HPV test should be given more often.

"Women need to ask to be screened for this potentially life-threatening virus before it is too late," she said.

"If there's this virus and I do have it or did have it, why didn't I know about it? They basically test you for everything when you get pregnant."

FDA approval of the HPV vaccine Gardasil, which provides immunity from two kinds of HPV that cause 70 percent of cervical cancer, has sparked increased interest in the virus from women and the media. The vaccine's maker, pharmaceutical company Merck, has started a national ad campaign to promote HPV awareness. Commercials show women talking about "cancer caused by a virus" and direct viewers to the website www.

tell-someone.com. The women in the commercial appear surprised, just like Wyse, to hear that HPV causes cervical cancer.

Mao has studied HPV for almost 10 years and treated the disease for much longer. She pointed out that while doctors have had an inexpensive test for cervical cancer, the Pap test, since the 1940s, they did not have a reliable test for HPV until the last decade.

"HPV has been very elusive," Mao said. "It was one of more difficult viruses to look at in the lab." In 2000, the FDA approved an HPV DNA test, but only as a diagnosis tool for women who had abnormal Pap test results. Even though the regulations relaxed a little in 2003, Mao said most doctors still use the HPV DNA test only to diagnose abnormal Pap results. That explains why, until the release of the vaccine, many women knew about cervical cancer, but few people had heard about HPV unless they were diagnosed with it.

Even in the absence of routine HPV screening, the Pap test helped doctors in the United States bring cervical cancer rates under control. Between 1955 and 1992, the number of U.S. cervical cancer deaths dropped by 74 percent, according to the American Cancer Society. Dr. Anna Giuliano, a researcher at the H. Lee Moffitt Cancer Center and Research Institute in Florida, has studied HPV and cervical cancer since completing her Ph.D. in 1990.

"Ultimately, as long as people participate in a Pap smear screening program, their risk for cancer is going to be very low," Giuliano said.

Cervical cancer ranks 11th on the list of common cancers in American women, according to the American Social Health Association. But worldwide, it is the second deadliest cancer, next to breast cancer, in women because developing countries lack Pap test screening programs.

The World Health Organization reports that 80 percent of the world's cervical cancers occur in developing countries in Asia, Africa, and Central America. In Central America and the Caribbean, cervical cancer is more common than breast cancer.

The Bill and Melinda Gates Foundation has funded some of the most well-known efforts to fight cervical cancer in developing countries. From 1999 to 2004, the foundation gave $50 million to establish and support the Alliance for Cervical Cancer Prevention, which works with local doctors and health agencies to set up screening programs in countries like Angola, India, and Tanzania.

In June, the nonprofit global health organization PATH announced it had received $27.8 million from the foundation for a five-year project to introduce the HPV vaccine in India, Peru, Uganda, and Vietnam. A spokeswoman for PATH said the organization had just started working on the project, and, like all global health programs, it would take a while to implement. Merck has promised to give projects like PATH's a discount on Gardasil.

In the United States, the vaccine is already for sale for $120 a dose, more expensive than any other vaccine on a price list published in August by the Centers for Disease Control.

Since it takes three doses to develop full immunity, American women can expect to pay $360 for full protection against HPV. Some private insurance companies have already agreed to cover the cost. So did the federal Vaccines for Children program, which provides free immunizations to uninsured or underinsured children. Since Pap testing, which usually costs less than $50 a test, has successfully kept U.S. cervical cancer at bay, Giuliano does not expect rates of the disease to drop significantly lower because of the vaccine. Rather, she predicted, the incidence of abnormal Pap tests and genital warts will decrease. Whether it will encourage promiscuity has not been tested.

"There have been studies looking at how women feel once they have been given an HPV test diagnosis," Giuliano said. "It's almost akin to having been diagnosed with one of the classic STDs. . . . Women don't know if they can have sex again or not. It does create a lot of anxiety even when they don't develop cervical cancer."

To develop immunity to HPV, women must receive the vaccine before they expose themselves to the disease. That puts the responsibility on parents to estimate when daughters will become sexually active and to decide whether and when a girl should get the HPV vaccine. The CDC recommended the vaccine for girls as young as 9, stirring a controversy similar to the debate over sex education in schools. States chose not to include the vaccine on their lists of shots required for school attendance.

Conservative family groups that oppose mandatory sex education and condom distribution at schools have said they support the use of the vaccine as long as parents, not schools, choose whether their children receive it. The Family Research Council issued the following statement:

"While we welcome medical advances such as an HPV vaccine, it remains clear that practicing abstinence until marriage and fidelity within marriage is the single best way of preventing the full range of sexually transmitted diseases, unwanted pregnancies, and negative psychological and emotional consequences that can result from sexual activity outside marriage."

Mao witnesses those consequences at the Harborview Women's Clinic, where every day she explains HPV to another patient who has never heard of it. "I've taken care of a lot of young women with fairly significant disease who end up getting procedures done to remove abnormal cells," Mao said. "I've had people tell me, 'I wish someone would have told me about HPV before I had sex with people, and maybe I would have had fewer partners or thought about it a little.' People don't understand the risk of having boyfriends when 15 or 16 years old other than just getting pregnant."